SARS-CoV-2 mRNA Vaccination in Patients With Hepatocellular Carcinoma Treated With Immune Checkpoint Inhibitors

Immune checkpoint inhibitors (ICIs) have become a cornerstone of systemic therapy for advanced hepatocellular carcinoma (HCC). Their efficacy, however, varies substantially between patients, and factors that modulate immunotherapy response remain incompletely understood .

Recent mechanistic and clinical data have raised the hypothesis that SARS-CoV-2 mRNA vaccines might augment responsiveness to ICIs. A landmark study by Grippin et al. demonstrated that mRNA vaccines induce a systemic surge of type-I interferons, activate antigen-presenting cells, increase PD-L1 expression on tumor cells, and ultimately sensitize tumors to ICIs across various malignancies including NSCLC (non-small cell lung cancer) and melanoma. In their retrospective cohorts, receiving a COVID-19 mRNA vaccine within 100 days before starting ICI was associated with significantly improved overall survival and progression-free survival While these findings suggest that COVID-19 mRNA vaccines may act as potent immune modulators in the context of immunotherapy, no data exist for HCC, a tumor entity that is characterized by an immunosuppressive, 'immune-cold' microenvironment that limits effective anti-tumor immune responses.

Given the widespread implementation of COVID-19 vaccination programs in Austria since 2021, and the large number of HCC patients receiving ICI-based therapies at tertiary centers, a rigorous retrospective analysis is now feasible.

Inclusion criteria

• Age ≥ 18 years
• Radiologically or histologically confirmed hepatocellular carcinoma
• Treatment with immune checkpoint inhibitor-based therapy (mono- or combination therapy; e.g., atezolizumab/bevacizumab, durvalumab/tremelimumab, nivolumab, pembrolizumab)
• Complete electronic medical records available
• At least one imaging-based response assessment using mRECIST

Exclusion criteria

• Missing key clinical data required for main analyses (e.g. survival status, date of progression, Child-Pugh class, BCLC stage)